phosphodiesterase inhibitors Flashcards
selective inhibition of PDE 3 decreases the breakdown of what?
cAMP
increased cAMP in the myocardium stimulates what to phosphorylate the SR?
protein kinases
the phosphorylated SR causes an increased influx of what?
Ca
increased Ca leads to an increase or decrease in myocardial contractility?
increase
increased cAMP in vascular SM increases or decreases available Ca?
decreases
increased cAMP in vascular SM decreases available Ca by facilitating the uptake of Ca by what?
SR
this uptake of Ca into the vascular SM’s SR causes the SM to do what and the vessels to do what?
relax, dilate
do selective PDE 3 inhibitors relax SM in the arteries, veins or both?
both
what is the combined effect of PDE 3 inhibitors?
positive inotrope with vascular SM relaxation
Do PDE 3 inhibitors increase or decrease these physiologic effects?
- contractility
- CO
- LVEDP
- venous capacity
- filling pressures (CVP, PCWP)
- venous return to the heart
- mean PAP
- pulmonary vascular resistance
- SVR
- increase
- increase
- decrease
- increase
- decrease
- decrease
- decrease
- decrease
- decrease
Amrinone has dose-dependent positive inotropic and vasodilator effects that increases what physiologic effect and decreases what physiologic effect?
CO, LVEDP
large fraction of Amrinone undergoes what 2 liver elimination processes? (NA, G)
N-acetylation and glucuronidation
what is the loading dose of Amrinone (mg/kg) and what is the maintenance infusion rate (mcg/kg/min)?
0.5-1.5 mg/kg; 2-10 mcg/kg/min
what are 3 SEs of Amrinone? (one with rapid infusion, one dose-related, one d/t increased myocardial Ca)
hypotension, thrombocytopenia, cardiac arrythmias
Amrinone causes dose-related thrombocytopenia by increasing cAMP in plts, which inhibits what sequence at several steps? (PAS)
plt activation sequence
milrinone is how many times more potent as an inotrope than amrinone?
30 times
in what 2 ways does milrinone improve CO?
increases inotropy, relaxes vascular SM
what is milrinone bolus dose (mcg/kg) given over how many minutes, which is followed by a continuous infusion of what rate (mcg/kg/min)?
50 mcg/kg over 10 minutes; 0.375-0.75 mcg/kg/min
what percent of milrinone is protein bound?
70%
what percent of milrinone is excreted unchanged by the kidneys?
80%
milrinone dose needs to be decreased in pts with what?
renal impairment
milrinone is useful in managing acute dysfunction of what such as after cardiac surgery?
acute LV dysfunction
milrinone enhances the weaning from what?
cardio-pulmonary bypass
milrinone can also be used as a bridge to what? (OHT)
orthotopic heart transplant
